Cutaneous Oncology, Moffitt Cancer Center , Tampa, FL, USA ; the Departments of Pathology and Cell Biology, University of South Florida , Tampa, FL, USA.
Sci Rep. 2012;2:765. doi: 10.1038/srep00765. Epub 2012 Oct 24.
We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20⁺ B cell follicles with prominent areas of CD3⁺ T cells (both CD4⁺ and CD8⁺ subsets). CD86⁺, but not FoxP3⁺, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.
我们已经在 14492 个不同的实体瘤的基因组阵列上检测了 12 种趋化因子基因表达谱(GES),并显示其在不同组织学中有广泛的分布。我们假设,这种 12 种趋化因子 GES 可能能够准确预测 IV 期(非局部区域)黑色素瘤转移中独特的肿瘤内免疫反应。12 种趋化因子 GES 预测存在独特的类似于淋巴结的结构,其中包含含有 CD20⁺B 细胞滤泡和突出的 CD3⁺T 细胞(CD4⁺和 CD8⁺亚群)区域。这些独特结构中也存在 CD86⁺,但不存在 FoxP3⁺细胞。12 种趋化因子 GES 评分与独特的淋巴结样结构的存在之间的直接相关性也与该亚组黑色素瘤患者的总体生存率提高相关。这种新型 12 种趋化因子 GES 的使用可能揭示肿瘤免疫反应原位机制的基本信息,从而可能提高对最适合免疫治疗的黑色素瘤患者的识别和选择。